Original ArticleSerum Levels of Risperidone and Its Metabolite, 9-Hydroxyrisperidone: Correlation Between Drug Concentration and Clinical ResponseLostia, Alfonso M PhD*; Mazzarini, Lorenzo MD†; Pacchiarotti, Isabella MD†; Lionetto, Luana PhD*; Rossi, Pietro De MD†; Sanna, Livia MD†; Sani, Gabriele MD†; Kotzalidis, Giorgio D MD†; Girardi, Paolo MD†; Simmaco, Maurizio MD*; Tatarelli, Roberto MD†Author Information From the *Dipartimento di Scienze Biochimiche “A. Rossi Fanelli,” Diagnostica Molecolare Avanzata and †Dipartimento di Neuroscienze, Unità Psichiatrica, Azienda Ospedaliera Sant'Andrea, II Facoltà di Medicina e Chirurgia, Sapienza Università di Roma, Rome, Italy. Received for publication November 15, 2008; accepted April 15, 2009. There is no financial connection with any devices, assays, or drugs that are discussed in the article and any connections with competing financial interests. Supported in part by grants from Sapienza Università di Roma and the Italian Ministero dell'Università e della Ricerca. Correspondence: Prof Maurizio Simmaco, MD, Dipartimento di Scienze Biochimiche “A. Rossi Fanelli,” Diagnostica Molecolare Avanzata, Azienda Ospedaliera Sant'Andrea, Via di Grottarossa 1035-00189 Rome, Italy (e-mail: [email protected]). Therapeutic Drug Monitoring: August 2009 - Volume 31 - Issue 4 - p 475-481 doi: 10.1097/FTD.0b013e3181aa4780 Buy Metrics Abstract The aim of this study was to assess a method able to analyze serum levels of risperidone (RIS) and its metabolite, 9-hydroxyrisperidone (9-OH-RIS), and to investigate possible relationships between changes in serum concentrations of these drugs and clinical measures, so to identify early markers of treatment response. The authors developed a sensitive and specific liquid chromatography-tandem mass spectrometry method to measure RIS and its metabolite in serum. Fifteen RIS-naive patients were admitted to an acute psychiatric care unit and treated with 4-6 mg/d oral RIS. At days 7 and 21 of hospital stay, serum levels were measured; clinical scales and serum prolactin were assessed. RIS and its metabolite were analyzed by a Q-Trap 2000 triple quadrupole/ion trap mass spectrometer in the multiple reaction-monitoring mode. Chromatographic separation was accomplished using a cyano column with an analytical run of 9 minutes. The calibration curve exhibited consistent linearity and reproducibility in the range 0-100 ng/mL for both analytes. Lower limit of quantification was 0.2 ng/mL; limit of detection, for a signal to noise ratio of 3, was 0.05 ng/mL for both analytes. Serum RIS and 9-OH-RIS levels increased at day 7, reaching a steady state, and remaining constant up to day 21. Scores on psychopathology rating scales decreased; serum prolactin and neurological rating scale for extrapyramidal effects rose at day 7 and remained stable thereafter. No correlation was found between serum concentration values, including sum and ratio of RIS and 9-OH-RIS, and any of the other clinical values (serum prolactin and clinical scales). These data indicate that clinical changes are related to the achievement of steady state levels of RIS and its metabolite and are maintained, but not continued, with continued RIS treatment. Therapeutic drug monitoring of RIS and its metabolites is not recommended as a routine procedure in patients with psychotic disorders. © 2009 Lippincott Williams & Wilkins, Inc.